Escitalopram, Sertraline Superior Treatments for Depression

Action Points

Explain to interested patients that escitalopram and sertraline were more efficacious and better tolerated than 10 other drugs in a meta-analysis of new-generation antidepressants.

Note that reboxetine was the least efficacious and least-tolerated drug in the meta-analysis.

VERONA, Italy, Jan. 28 -- For the acute treatment of major depression, escitalopram (Lexapro, Cipralex) and sertraline (Zoloft, Lustral) may be better than other commonly prescribed antidepressants, researchers here said.

These two drugs were more efficacious and better tolerated than others in a review of 12 new-generation antidepressants, Andrea Cipriani, M.D., of the University of Verona, and colleagues reported online in The Lancet.

"The most important clinical implication of the results is that escitalopram and sertraline might be the best choice when starting a treatment for moderate to severe major depression because they have the best possible balance between efficacy and acceptability," the researchers said.

Previous studies have shown inconsistent results for the efficacy and acceptability of second-generation antidepressants, many of which are structurally related and share similar mechanisms of action.

In terms of acceptability, escitalopram, sertraline, citalopram, and bupropion were better tolerated than the other new-generation antidepressants, indicating that two of the most efficacious treatments -- mirtazapine and venlafaxine -- may not be the best overall treatments.

Because they topped the list for both efficacy and acceptability, the researchers said escitalopram and sertraline may be the top treatments for during the eight-week acute phase of depression.

Going a step further, the researchers recommended sertraline over escitalopram because it costs less in most countries.

"Sertraline is off patent and escitalopram is still branded . . . and we felt the bottom line was to prescribe the cheapest [medication]," Dr. Cipriani said.

However, they didn't perform a formal cost-analysis, so they cannot make their recommendation "unequivocally because several other costs are associated with the use of antidepressants."

Reboxetine, fluvoxamine, paroxetine, and duloxetine were the least efficacious and least-tolerated drugs, making them less favorable options for treatment, the researchers said.

Furthermore, reboxatine was the least tolerated agent and was significantly less effective than all the other drugs.

Dr. Cipriani said he would not prescribe reboxetine as a first-line treatment in his patients. However, he emphasized that if patients are responding well to the drug, there is no need to take them off it.

Dr. Cipriani also noted that reboxetine is the only norepinephrine reuptake inhibitor assessed in their review. Buproprion is a norepinephrine-dopamine reuptake inhibitor, and the other 10 are selective serotonin reuptake inhibitors (SSRIs).

He said that may account for some difference, although it is still highly speculative. Even among the SSRIs, he said, "it is strange they score so differently because they have the same mechanism of action."

"It is still unclear why there are differences between drugs that are closely related," he added.

The researchers noted that a limitation of their review may be the presence of sponsorship bias in the trials they evaluated because most were funded by the pharmaceutical companies that marketed the drugs.

In an accompanying editorial, Sagar V. Parikh, M.D., of the University of Toronto, said the study sets "a new gold standard of reliable information."

"By raising the efficacy bar beyond 'beating placebo,' they hope to discourage the development of drugs of routine efficacy and also side-step the ethically challenging position of using placebos in an era of multiple proven treatments for depression," Dr. Parikh said.

"With such a host of clinical and research implications, this pivotal meta-analysis of antidepressant efficacy and acceptability will surely change the tune of psychiatrists," he noted.

Dr. Cipriani reported no conflicts of interest.

A co-author has received research funding from GlaxoSmithKline, sanofi-aventis, the U.K. Department of Health and Medical Research Council, the Stanley Medical Research Institute, and advisory committee payments from Bristol Myers Squibb.

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